Rhizolutin, a Novel 7/10/6-Tricyclic Dilactone, Dissociates Misfolded Protein Aggregates and Reduces Apoptosis/Inflammation Associated with Alzheimer's Disease.
Alzheimer Disease
/ drug therapy
Amyloid beta-Peptides
/ antagonists & inhibitors
Animals
Apoptosis
/ drug effects
Inflammation
/ drug therapy
Mice
Mice, Transgenic
Neuroglia
/ drug effects
Neurons
/ drug effects
Neuroprotective Agents
/ chemistry
Plaque, Amyloid
/ drug therapy
Protein Aggregates
/ drug effects
Streptomyces
/ chemistry
tau Proteins
/ antagonists & inhibitors
Alzheimer's disease
amyloid β
lactones
natural products
tau protein
Journal
Angewandte Chemie (International ed. in English)
ISSN: 1521-3773
Titre abrégé: Angew Chem Int Ed Engl
Pays: Germany
ID NLM: 0370543
Informations de publication
Date de publication:
14 12 2020
14 12 2020
Historique:
received:
06
07
2020
revised:
20
08
2020
pubmed:
28
8
2020
medline:
23
3
2021
entrez:
27
8
2020
Statut:
ppublish
Résumé
Rhizolutin (1) was discovered as a natural product of ginseng-rhizospheric Streptomyces sp. WON17. Its structure features an unprecedented 7/10/6-tricyclic dilactone carbon skeleton composed of dimethylcyclodecatriene flanked by a 7-membered and a 6-membered lactone ring based on spectroscopic analysis. During an unbiased screening of natural product libraries, this novel compound was found to dissociate amyloid-β (Aβ) plaques and tau tangles, which are key pathological hallmarks of Alzheimer's disease (AD). Rhizolutin treatment of APP/PS1 double transgenic mice with AD significantly dissociated hippocampal plaques. In vitro, rhizolutin substantially decreased Aβ-induced apoptosis and inflammation in neuronal and glial cells. Our findings introduce a unique chemical entity that targets Aβ and tau concurrently by mimicking misfolded protein clearance mechanisms of immunotherapy, which is prominently investigated in clinical trials.
Identifiants
pubmed: 32844539
doi: 10.1002/anie.202009294
doi:
Substances chimiques
Amyloid beta-Peptides
0
Neuroprotective Agents
0
Protein Aggregates
0
tau Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
22994-22998Informations de copyright
© 2020 Wiley-VCH GmbH.
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